Understanding the molecular mechanisms of macrophage polarization and metabolic reprogramming in endometriosis: A narrative review

Abstract

Background Endometriosis is an estrogen‐dependent disease and causes pelvic pain and infertility. The limits of current pharmacotherapy in women who desire to become pregnant prompt the development of various targeted molecules for more effective treatment. A review article focused on the unique aspect of cellular metabolic reprogramming of endometriotic cells has been reported. The cellular metabolic pathways are reprogrammed to adapt to a variety of environmental stresses (e.g., nutrient starvation or glucose deprivation, hypoxic stress, excessive reactive oxygen species generation, and other environmental factors). This review aims to summarize macrophage polarization and metabolic reprogramming in endometriosis. Methods A literature search was performed between January 2000 and March 2022 in the PubMed and Google Scholar databases using a combination of specific terms. Results Macrophage cellular metabolism has a marked influence on its phenotype and function. Preclinical studies showed that metabolic conversion toward glycolysis or oxidative phosphorylation drives macrophage polarization to M1 or M2 phenotype, respectively. Such cellular metabolic rewiring can offer new therapeutic opportunities. Conclusion A better understanding of metabolic reprogramming biology in endometriosis‐associated macrophages is essential in considering novel therapeutic approach for endometriosis. However, there are currently no detailed studies on therapeutic strategies targeting the cellular metabolic properties of endometriosis‐associated macrophages.

Chronic Stress Blocks the Endometriosis Immune Response by Metabolic Reprogramming

“…Studies have shown that metabolism can affect the progress of endometriosis. TGF-1 and lactate levels of endometriosis patients are significantly higher than in normal females, and, in particular, the lesions of the disease are highly expressed in glycolytic-related genes, such as HIf1-α, Glut1, Pdk1, and Ldha, as well as the expression of glycolytic related genes; the glycolytic metabolism of the heterotopic endometrium was transferred to the warfarin effect [ 46 , 47 ]. Our study also found that chronic stress alters the microenvironment of endometrium cells and affects their implantation and invasion by affecting multiple metabolic pathways in the lesions of patients with endometriosis.…”

Macrophage polarization in adenomyosis: A review

“…17 It is widely recognized that M1 macrophages are triggered by pathogens, lipopolysaccharide (LPS), interferon-gamma (IFN-γ), tumor necrosis factor-alpha (TNF-α), and granulocyte macrophage-colony stimulating factor (GM-CSF), whereas M2 macrophages are typically activated by factors, such as interleukin (IL)−4, IL-10, IL-13, transforming growth factor-beta (TGF-β), and immune complexes. 18 Regarding function, M1 macrophages, also known as pro-inflammatory macrophages, can promote inflammation, eliminate pathogenic microorganisms, and combat tumors by secreting various pro-inflammatory factors, such as IL-1β, IL-6, and TNF-α. In contrast, M2 macrophages are anti-inflammatory macrophages that produce a large number of anti-inflammatory factors, such as IL-10, TGF-β, and arginase.…”

“…Conventionally, naive macrophages (M0) are classified into classically activated macrophage (M1) and the alternatively activated macrophage (M2) based on their function and activation state 17 . It is widely recognized that M1 macrophages are triggered by pathogens, lipopolysaccharide (LPS), interferon‐gamma (IFN‐γ), tumor necrosis factor‐alpha (TNF‐α), and granulocyte macrophage‐colony stimulating factor (GM‐CSF), whereas M2 macrophages are typically activated by factors, such as interleukin (IL)−4, IL‐10, IL‐13, transforming growth factor‐beta (TGF‐β), and immune complexes 18 . Regarding function, M1 macrophages, also known as pro‐inflammatory macrophages, can promote inflammation, eliminate pathogenic microorganisms, and combat tumors by secreting various pro‐inflammatory factors, such as IL‐1β, IL‐6, and TNF‐α.…”

Association between exposure to polycyclic aromatic hydrocarbons and endometriosis: data from the NHANES 2001–2006

“…Endometriosis is associated with a 50% increase in the risk of epithelial ovarian cancer ( 6 ), and is also correlated with gastrointestinal and immunological diseases and thyroid cancer ( 7 ). Endometriosis is an estrogen-dependent disease, which can be affected by genetics, environmental factors, and the immune system ( 8 , 9 ).…”